{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T03:41:32Z","timestamp":1793418092358,"version":"4.5.0"},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The interplay between circadian rhythms and epilepsy has gained increasing attention. The suprachiasmatic nucleus (SCN), which acts as the master circadian pacemaker, regulates physiological and behavioral rhythms through its complex neural networks. However, the exact role of the SCN and its\n                    <jats:italic>Bmal1<\/jats:italic>\n                    gene in the development of epilepsy remains unclear. In this study, we utilized a lithium\u2013pilocarpine model to induce epilepsy in mice and simulated circadian disturbances by creating lesions in the SCN and specifically knocking out the\n                    <jats:italic>Bmal1<\/jats:italic>\n                    gene in the SCN neurons. We observed that the pilocarpine\u2010induced epileptic mice experienced increased daytime seizure frequency, irregular oscillations in core body temperature, and circadian gene alterations in both the SCN and the hippocampus. Additionally, there was enhanced activation of GABAergic projections from the SCN to the hippocampus. Notably, SCN lesions intensified seizure activity, concomitant with hippocampal neuronal damage and GABAergic signaling impairment. Further analyses using the Gene Expression Omnibus database and gene set enrichment analysis indicated reduced\n                    <jats:italic>Bmal1<\/jats:italic>\n                    expression in patients with medial temporal lobe epilepsy, potentially affecting GABA receptor pathways. Targeted deletion of\n                    <jats:italic>Bmal1<\/jats:italic>\n                    in SCN neurons exacerbated seizures and pathology in epilepsy, as well as diminished hippocampal GABAergic efficacy. These results underscore the crucial role of the SCN in modulating circadian rhythms and GABAergic function in the hippocampus, aggravating the severity of seizures. This study provides significant insights into how circadian rhythm disturbances can influence neuronal dysfunction and epilepsy, highlighting the therapeutic potential of targeting SCN and the Bmal1 gene within it in epilepsy management.\n                  <\/jats:p>","DOI":"10.1111\/jpi.12993","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T03:11:00Z","timestamp":1721963460000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Dysregulation of the Suprachiasmatic Nucleus Disturbs the Circadian Rhythm and Aggravates Epileptic Seizures by Inducing Hippocampal GABAergic Dysfunction in C57BL\/6 Mice"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1039-4467","authenticated-orcid":false,"given":"Xiaoshan","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotao","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The Afflliated Traditional Chinese Medicine Hospital of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuewen","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieli","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqin","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3218-7231","authenticated-orcid":false,"given":"Wei","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Nanfang Hospital Southern Medical University  Guangzhou China"},{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao0318"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm1962"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.05.045"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1226339"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00577-7"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(21)00034-1"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30335-1"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32596-0"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.5370"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00464-1"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.09.044"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14513"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16716"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-022-04154-0"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2017.05.014"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2014.00121"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-021-00824-4"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat4104"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2301330120"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0483-6"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17336"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/39908"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0471-2"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14343"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1292-0"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6535-10.2011"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2016.03.1050"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro-2019-0088"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2009.00683.x"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2158-19.2020"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac293"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15769"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14336"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2021.08.020"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51880"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2015.12.005"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20172347"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00632"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2012.03577.x"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1449-15.2015"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.30773\/pi.2018.01.18.2"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aat5979"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-021-00824-4"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16796"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-023-01025-4"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00027.2019"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.282079"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12576-018-0604-x"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115729109"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1177\/0748730411415363"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adj1010"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI70317"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03407-7"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/0013-4694(75)90204-7"},{"key":"e_1_2_10_56_1","first-page":"293","article-title":"Animal Models of Epilepsy and Progressive Effects of Seizures","volume":"97","author":"Cortez M. A.","year":"2006","journal-title":"Advances in Neurology"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00211.2020"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.577623"}],"container-title":["Journal of Pineal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12993","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T03:02:16Z","timestamp":1727146936000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpi.12993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":57,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/jpi.12993"],"URL":"https:\/\/doi.org\/10.1111\/jpi.12993","archive":["Portico"],"relation":{},"ISSN":["0742-3098","1600-079X"],"issn-type":[{"value":"0742-3098","type":"print"},{"value":"1600-079X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,26]]},"assertion":[{"value":"2024-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12993"}}